Porphyrin functionalization has long been of great interest in the chemistry community because of the vast potentials and demands for porphyrin derivatives in diverse fields such as materials, supramolecular chemistry, and biomimetic models. Particularly, aryl nitration of meso-tetraphenylporphyrin (abbreviated as H2TPP) has been attractive since H2TPP is commercially available and the diversity of nitro-group substitution makes it a great synthetic scaffold for sophisticated porphyrin arrays.
More than 20 years ago, Kruper and coworkers reported a simple process to afford a series of highly substituted derivatives based upon electrophilic aromatic substitution of H2TPP using red fuming nitric acid (Scheme 1). But, this approach, while successfully in producing mono-, di-, and tri-substituted species (compounds 1-4), but no one has been able to obtain the tetra-nitro products (compound 5) in a meaningful yield. Meng et al. later studied the effect of time on the similar nitration reactions and revealed that a trace quantity of 5 (˜2% yield with impurities) can be obtained while the reaction time was extended to 2 days. However, further prolonging the reaction time ended up with failure only. The absence or a very low level of 5 observed in the reactions was usually understood as a result of macrocyclic degradation. Recently, a modified process having an improved yield of 2 was described by Ostrowski et al. using yellow fuming nitric acid, but still no 5 can be detected.

Prior to the present invention, for synthesis of tetrakis(p-nitro-aryl)porphyrins, the best known methods in the art rely on either Rothermound or Lindsey's condensations. However, the methods usually involve multi-step sequences that require extensive separation steps. The yield of the products is often very low. Due to the vast interest in porphyrin functionalization, there is a long felt need for developing method for efficient production of tetra-derivative of H2TPP in an industrial scale.